Prenatal nicotine exposure alters pulmonary function in newborn rhesus monkeys
Prenatal nicotine exposure alters pulmonary function in newborn rhesus monkeys
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DOI：
10.1164/ajrccm.164.6.2011097
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发表时间：
2001-09-15
影响因子：
24.7
通讯作者：
Spindel, ER
中科院分区：
文献类型：
--
作者：
Sekhon, HS;Keller, JA;Spindel, ER
流行病学研究表明，怀孕期间吸烟的妇女的后代肺功能异常，并伴有较高的下呼吸道疾病发病率。最近胎儿肺中尼古丁乙酰胆碱受体（nAChR）的鉴定表明，尼古丁与胎儿肺中nAChR的直接相互作用可能是这些婴儿出生后肺部异常的基础。这一假设在猴子身上进行了测试，以确定母体尼古丁暴露是否会导致新生猴子肺部力学的变化，类似于在母体怀孕期间吸烟的人类婴儿身上观察到的变化。从妊娠第26天至第160天，用皮下渗透泵给定时怀孕的恒河猴注射尼古丁（1.5 mg/kg/d, n = 7）或生理盐水（n = 7）。妊娠第160天（足月165 d）剖宫产，次日行肺功能检查。实验结束后，动物被处死，肺部称重并固定。在子宫内尼古丁暴露后，肺重量和固定肺体积显著下降（分别为16%和14%）。妊娠期暴露于尼古丁的新生儿呼气峰潮流量、FEV0.2、平均呼气中流量、呼气峰用力量（FEVPEF）和FEVPEF/FVC%均显著降低。绝对和特定肺阻力显著增加，而绝对和特定动态顺应性在产前尼古丁处理的幼崽中保持不变。这些肺功能的变化与在人类吸烟者后代中观察到的变化惊人地相似。这表明尼古丁与nAChR在肺部发育中的相互作用是导致母亲在怀孕期间吸烟的婴儿肺部力学改变的原因。
Epidemiological studies have shown that offspring of women who smoke during pregnancy have abnormal lung function and associated higher incidences of lower respiratory disorders. The recent Identification of nicotinic acetylcholine receptors (nAChR) in fetal lung suggests that the direct interaction between nicotine and nAChR in fetal lung may underlie the postnatal pulmonary abnormalities seen in such infants. This hypothesis was tested in monkeys to determine if maternal nicotine exposure would produce changes in lung mechanics in newborn monkeys similar to those observed in human infants whose mothers smoked during pregnancy. Timed pregnant rhesus monkeys were Infused with either nicotine (1.5 mg/kg/d, n = 7) or saline (n = 7) using subcutaneous osmotic pumps from Day 26 to 160 of gestation. On Day 160 of pregnancy (term = 165 d), fetuses were delivered by C-section, and the following day were subjected to pulmonary function testing. After testing, animals were sacrificed, and lungs weighed and fixed. Lung weight and fixed lung volume decreased (16% and 14%, respectively) significantly following in utero nicotine exposure. Peak tidal expiratory flow, FEV0.2, mean mid-expiratory flow, forced expiratory volume at peak expiratory flow (FEVPEF), and FEVPEF/FVC% were significantly lower in newborns exposed to nicotine during gestation. Absolute and specific pulmonary resistance increased significantly whereas absolute and specific dynamic compliance remained unchanged in prenatally nicotine-treated pups. These changes in pulmonary function are strikingly similar to the changes observed in offspring of human smokers. This suggests that the interaction of nicotine with nAChR in developing lung Is responsible for the altered pulmonary mechanics observed in human infants whose mothers smoked during pregnancy.